Is ANKRD16 p.Ala21Ser (c.61G>T) pathogenic?

ANKRD16 p.Ala21Ser (c.61G>T) is classified Uncertain significance in ANKRD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.1038); Ultra-rare (popmax 0.0109%, nfe).

How common is ANKRD16 p.Ala21Ser (c.61G>T) in the general population?

ANKRD16 p.Ala21Ser (c.61G>T) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

What do computational predictors say about ANKRD16 p.Ala21Ser (c.61G>T)?

AlphaMissense predicts likely benign (score 0.1038) — an in-silico prediction, not a clinical call.

ANKRD16 p.Ala21Ser

c.61G>T · VCV3867006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1038	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.54, phastCons 0.021
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	9.098	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% European (non-Finnish) · 117/1,071,218 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00867%

Overall 0.00876% 121/1,381,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,156
Remaining individualsnot grpmax-eligible	0.00574%	17,413
Admixed American	0.00334%	29,916

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANKRD16
Protein: p.Ala21Ser
Coding: c.61G>T
MANE Select: NM_019046
Type: single nucleotide variant
Location: chr10:5889294 (GRCh38)
Gene constraint: LOEUF 1.356 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32

Full ANKRD16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD16 p.Ala208Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala234Ser Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala240Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala359Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala36Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Arg146Gln Uncertain significance ★ ⚠ same type
ANKRD16 p.Arg20Leu Uncertain significance ★ ⚠ same type
ANKRD16 p.Arg347Gly Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ankrd16-p-ala21ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown